AICDA drives epigenetic heterogeneity and accelerates germinal center-derived lymphomagenesis

Matt Teater, Pilar M. Dominguez, David Redmond, Zhengming Chen, Daisuke Ennishi, David W. Scott, Luisa Cimmino, Paola Ghione, Jayanta Chaudhuri, Randy D. Gascoyne, Iannis Aifantis, Giorgio Inghirami, Olivier Elemento (), Ari Melnick () and Rita Shaknovich ()
Additional contact information
Matt Teater: Weill Cornell Medicine
Pilar M. Dominguez: Weill Cornell Medicine
David Redmond: Weill Cornell Medicine
Zhengming Chen: Weill Cornell Medicine
Daisuke Ennishi: British Columbia Cancer Agency
David W. Scott: British Columbia Cancer Agency
Luisa Cimmino: NYU School of Medicine
Paola Ghione: Weill Cornell Medicine
Jayanta Chaudhuri: Gerstner Sloan-Kettering Graduate School
Randy D. Gascoyne: British Columbia Cancer Agency
Iannis Aifantis: NYU School of Medicine
Giorgio Inghirami: Weill Cornell Medicine
Olivier Elemento: Weill Cornell Medicine
Ari Melnick: Weill Cornell Medicine
Rita Shaknovich: Weill Cornell Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: Abstract Epigenetic heterogeneity is emerging as a feature of tumors. In diffuse large B-cell lymphoma (DLBCL), increased cytosine methylation heterogeneity is associated with poor clinical outcome, yet the underlying mechanisms remain unclear. Activation-induced cytidine deaminase (AICDA), an enzyme that mediates affinity maturation and facilitates DNA demethylation in germinal center (GC) B cells, is required for DLBCL pathogenesis and linked to inferior outcome. Here we show that AICDA overexpression causes more aggressive disease in BCL2-driven murine lymphomas. This phenotype is associated with increased cytosine methylation heterogeneity, but not with increased AICDA-mediated somatic mutation burden. Reciprocally, the cytosine methylation heterogeneity characteristic of normal GC B cells is lost upon AICDA depletion. These observations are relevant to human patients, since DLBCLs with high AICDA expression manifest increased methylation heterogeneity vs. AICDA-low DLBCLs. Our results identify AICDA as a driver of epigenetic heterogeneity in B-cell lymphomas with potential significance for other tumors with aberrant expression of cytidine deaminases.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-017-02595-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02595-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-02595-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().